There have been many attempts in the pharmaceutical industry to control drug release and maintain drug concentration in the blood at an appropriate level for a long period of time. In order to maintain drug concentration in the blood at an appropriate level for a long period of time, a pharmaceutical advancement (release control) to maintain drug absorption for a long time is necessary. Such release-controlled pharmaceutical preparations are referred to as “sustained-release preparations”.
Sustained-release preparations are defined as pharmaceutical preparations in which the release rate, release time, and release location of the pharmaceutically active ingredient are controlled with the purpose of reducing the frequency of administration, or decreasing side effects. Immediate-release preparations are defined as pharmaceutical preparations whose pharmacologically active substance release is not particularly controlled. For example, with respect to oral preparations, water-insoluble matrix-type, hydrogel matrix-type, film coating-type, osmotic pump-type, or like sustained-release preparations are widely known.
Immediate-release preparations and sustained-release preparations can be classified according to the length of disintegration time of the pharmaceutical preparation, instead of whether the release is controlled or not. More specifically, immediate-release preparations disintegrate in a short time and immediately release a pharmacologically active substance. Sustained-release preparations disintegrate over a long period of time and gradually release a pharmacologically active substance. To control the disintegration rate of a pharmaceutical preparation, the incorporation of a disintegrant into the pharmaceutical preparation is important. To obtain a desired disintegration rate, the selection of an optimal disintegrant is also important. Disintegration induced by disintegrants can be roughly classified into two types: swelling and capillary action (wicking). Swelling-type disintegrants disintegrate pharmaceutical preparations with their excellent water absorption and swelling capabilities. In contrast, wicking-type disintegrants cause water to quickly penetrate into pores in the pharmaceutical preparation to break the bonds between particles, thus dispersing the particles.
However, each type of disintegrants, i.e., swelling-type disintegrants and wicking-type disintegrants, has disadvantages. Since even a small amount of swelling-type disintegrant is highly effective in quickly causing the internal disintegration of pharmaceutical preparations, disintegrants of this type are unsuitable for prolonged disintegration control, i.e., sustained release. Wicking-type disintegrants have a low swelling ability and are thus less likely to cause internal disintegration of pharmaceutical preparations. However, even a slight decrease or increase in the amount of wicking-type disintegrant may result in insufficient disintegration or disintegration behavior similar to that of immediate-release pharmaceutical preparations. That is, precise adjustment of the amount of wicking-type disintegrant is difficult.
It is thus extremely difficult to achieve sustained release by controlling disintegration through mere selection of a disintegrant and mere adjustment of the amount of disintegrant used.